Wednesday, February 21, 2018

The Tisch MS Research Center of New York (click here) will soon begin its first-ever FDA approved Phase 2 regenerative stem cell study for multiple sclerosis. Last week, I published the first part of my interview with Dr. Saud Sadiq, the Director and Lead Research Scientist of The Center, which discussed the Phase 1 study and its results (click here). As promised, here is the second part of our discussion, which focuses on the upcoming Phase 2 study, the Tisch Center's new stem cell laboratories, how stem cells might help repair damaged nervous system tissues, and some of the other multiple sclerosis research projects being conducted by Tisch Center researchers and scientists.
This interview has been lightly edited for readability, and I’ve added some “WK Notes,” which attempt to translate overly complicated medical jargon into plain English.

WK: The Tisch center is now preparing to embark on Phase 2 of your MS stem cell trial. When do you expect this next phase of the study to get started?

Dr. Sadiq: After the Phase 1 study ended, we made a commitment at The Tisch Center that we needed to make our stem cell laboratories absolutely state-of-the-art. We’ve invested heavily in building a new stem cell lab, which is being completed now. Everything’s automated, it’s a next generation stem cell facility that will be functional and certified in about a month and a half. Then we will be prepared to start the Phase 2 study. We do still need some additional funding for Phase 2. We are applying to the National Multiple Sclerosis Society for a grant. Though they didn’t support Phase 1, given the impressive results of that trial we are hopeful that they will support us as we go forward. We also expect private contributions to help fund Phase 2, as these have always been the lifeblood of the foundation.

WK: How many patients will be involved in the Phase 2 study?

Dr. Sadiq: There will be 50 patients involved. It will be a double-blinded crossover study specifically designed to establish the effectiveness of the neural progenitor stem cells we've developed in our laboratories. So it has an entirely different aim than the Phase 1 sstudy, which was intended primarily to determine the safety and tolerability of our stem cell procedures. We are going to give Phase 2 study participants six treatments, one every two months. Therefore there will be more treatments given in greater frequency than in the Phase 1 study.

WK: So, with 50 patients, 25 will be getting actual stem cells, and 25 will be getting placebo treatments?

Dr. Sadiq: Yes, in the first year 25 subjects will get treatment and 25 will get placebo, and in the second year the ones who got placebo will get treatment and vice versa.

WK: What will the patient population look like for this Phase 2 trial?

Dr. Sadiq: The patients for this trial will have to meet much tighter inclusion criteria then the patients in Phase 1. They all must be diagnosed with SPMS or PPMS. They have to be ambulatory, so they’ll all have EDSS scores between 3 and 6.5. The FDA is requiring that we have an equal distribution of the EDSS scores. So there will be equal numbers of patients distributed between all the points along the EDSS scale. The other limitation is that all patients will need to have had the disease for 15 years or less.

WK: Will the study participants continue with their disease modifying drugs?

Dr. Sadiq: Yes, but they can’t have switched medications within six months from the start of the trial.

WK: Once they are in the trial they’ll have to remain on the same DMD for the duration of the study?

Dr. Sadiq: Yes.

WK: What will be the total duration of this trial?

Dr. Sadiq: There will be two years of study and placebo, and one year of follow-up. So a total of three years.

WK: Just to be clear, in the third year none of the patients will be receiving stem cells?

Dr. Sadiq: That’s correct, in the third year there will be no stem cells and no placebos. After the second year, all patients will have received six treatments. The patients who received stem cells in the first year will have placebo in the second year, and the patients who received placebo in the first year will receive stem cells in the second. The third year will be for observation of all patients.

WK: For all the folks out there with RRMS, if the Phase 2 trial proves successful then the stem cell protocol developed at Tisch could be applied to them as well, correct?

Dr. Sadiq: For patients with relapsing-remitting disease who experience a relapse that results in damage from which they don’t recover, stem cells could be introduced in an attempt to repair that damage. That would be the dream scenario, and it could render disability resulting from MS a thing of the past. But at this point were getting ahead of ourselves…

WK: As we move forward into a world in which stem cell treatments for MS become a standard of care, would you anticipate that patients will need continued and repeated stem cell treatments to maintain or advance whatever benefits they realize until a cure is finally found for multiple sclerosis?

Dr. Sadiq: Yes, that’s likely. I think the Phase 2 trial will really go a long way towards answering that question. It will be important to ascertain what happens to patients in the years after they receive their stem cells. Do they maintain their benefits, do they return to baseline, or do they fall somewhere in the middle? These will be significant findings. The design of this crossover trial will allow us to figure that out. My feeling going in is that patients will need stem cell treatments over the long-term, maybe not six a year after the initial treatment., but perhaps less frequently to maintain whatever improvement is seen.

WK: The neural progenitor cells developed by the Tisch Center – or any regenerative stem cells, for that matter – don’t directly address the disease process, correct? If so, does the disease remain active despite the use of these stem cells?

Dr. Sadiq: Yes, that’s right, the cells are not a cure for the disease. They hopefully secrete trophic factors that would stimulate the body’s own progenitor cells to activate and induce repair at sites of injury. (WK Note: trophic factors are elements which cause the body to maintain or start some action, in this case repairing damaged nerve cells and possibly affording some protection against attack from immune cells.)

WK: So, the stem cells may not necessarily repair injury all by themselves, but they may jumpstart natural repair mechanisms within the bodies of the patients in which they are implanted?

Dr. Sadiq: I think that’s the most likely mechanism. Whether they play some direct role is something we have to figure out, but I think it’s more likely that they’ll turn on a patient’s own progenitors and also create a trophic environment that acts as a shield from the immune system and allows the body to make repairs.

WK: I know that stem cells aren't the only focus of the Tisch Center's researchers and scientists. I’d like to touch on The Tisch Multiple Sclerosis Research Center of New York itself, and some of the other areas of research that are currently ongoing in The Center’s labs. Could you give us a peek inside and tell us about some of the other projects Tisch researchers are working on?

Dr. Sadiq: Well, at the Tisch Center our original goal was to identify the root cause of the disease. It may be some type of immune cell, or some unidentified infectious agent, or maybe some other environmental element. Once we can identify the cause of multiple sclerosis, we can then methodically work towards a cure. And finding a cure is our ultimate goal.

WK: So, the Tisch Center currently has researchers who spend their days searching for the root cause of multiple sclerosis?

Dr. Sadiq: Yes, absolutely. I try to focus on the real challenges that I see as a clinician treating patients every day. My focus is on trying to understand primary progressive MS, which is perhaps the most challenging form of MS as far as treatment is concerned. There are very few treatments that can alter the course of progressive MS. We’ve created an animal model in our lab to try to understand the mechanisms of progression and why remyelination does not take place at all in this form of the disease. In relapsing-remitting MS we see damage occur and then some repairs get made by the body, especially in early disease. This is something not seen in progressive MS. We need to understand the mechanisms of progression better. We are also focused on cognition dysfunction because that can really dehumanize the patients who suffer from severe cognitive deficits.

We are also hard at work identifying biomarkers that can indicate the activity and severity of the disease. We’ve published a lot of papers in this area. We are doing a lot of work on metabolic dysfunction in the central nervous system in MS, and hopefully, that will lead us to readily identify markers that can pinpoint progression and disease activity, which will, in turn, allow us to assess the effectiveness of treatments in individual patients. In conjunction to the Phase 2 stem cell study itself, one of our aims is to analyze the spinal fluid of all of the study participants for markers that may predict which patients are going to get better by Identifying which patients experience actual repair and remyelination. The goal of identifying biomarkers is to be able to tailor treatments to each individual patient, specific to them and the intricacies of their disease. MS is a very heterogeneous illness, meaning that it affects each patient differently. Through the use of biomarkers, we hope to be able to address these differences on a patient by patient basis.

WK: The Tisch Center is not affiliated with any hospital or academic institution, correct, so it’s an entirely independent research entity?

Dr. Sadiq: Yes we are completely independent. We run Tisch like an academic center in every regard. We have guest speakers and all of the activities that would be associated with typical University research centers, but we are not affiliated with any academic centers. We retain absolute independence in choosing our areas of research.

WK: If you don’t have any of these affiliations, how is all of the research we’ve discussed funded?

Dr. Sadiq: We rely entirely on grants and donations. We use almost all the funds raised directly for research. Fully 90% of all monies raised goes directly into research, which is really an extraordinarily high number compared to other organizations. We keep expenses very low, so only a small percentage of funds raised go towards administrative costs and other such overhead. All of our tax forms and documentation in this regard are available online.

WK: My understanding is that you are not currently receiving any funding at all from the National Multiple Sclerosis Society. Is this correct?

Dr. Sadiq: Yes, that's right, we’ve had some bad luck with the MS Society, but they promised to look into our Phase 2 study, and I’m putting in a grant application. Hopefully, this time they’ll get involved.

WK: Obviously, the Tisch family (click here) is involved, but where does the rest of the Center’s funding generally come from?

Dr. Sadiq: The Tisch family is a very big supporter, but so are our patients and their loved ones. We have a very loyal following of patients and their families and other supporters that really enable this to happen. They’ve been supporting us for close to two decades, even before we were formed as an independent center.

WK: How much is this Phase 2 trial going to cost?

Dr. Sadiq: The build-out of the laboratory cost $5 million, and that’s a done deal. The trial itself calls for another $4 million, and we are currently raising funds for the study itself.

WK: So funding is still needed for the Phase 2 trial?

Dr. Sadiq: Yes.

WK: Well, speaking strictly for myself as a patient who has been ravaged by this disease, I can’t think of any cause more important and worthy of donations.

Dr. Sadiq: That’s very kind. Maybe I should hire you as a fundraiser…

WK: You can pay me in stem cells… Even though I know I don’t qualify for the trial because of my level of disability…

Dr. Sadiq: That’s true, but don’t ever lose hope. Every day researchers here at Tisch and others around the world are working hard towards solving the puzzle of MS. I’m personally obsessed with curing multiple sclerosis.

As a patient of Dr. Sadiq’s, I can attest to his obsession with curing the disease. The man works at least six out of every seven days and even has a bedroom behind his office at the clinic affiliated with the Tisch Center. The clinic is called The International Multiple Sclerosis Management Practice (click here). I’m also acquainted with some of the researchers at the Tisch Center, who are so dedicated that they'll even put up with my incessant questions when I manage to corner one of them with my wheelchair.

For those interested in donating to the Tisch Center, you can learn about the various ways to contribute by (clicking here). If you’d like to encourage the National Multiple Sclerosis Society to get behind the first ever FDA approved Phase 2 MS stem cell trial with a nice big grant, here’s a webpage with contact info for all of the Society’s senior leadership (click here). Please be polite If you do reach out to the NMSS. As my grandmother always told me, you can catch more flies with honey than you can with vinegar…

7 comments:

To bad for the scale of the EDSS required for phase 2 otherwise you could have got in on it. Like most research its painfully slow. 3 years will be to late for some. I like the research though and the principle of the process. I think it holds more promise than the dramatic risky HSCT process.

So, I am a Multiple Sclerosis and Multiple Myeloma patient. I had an Auto Stem Cell Transplant in 2014. We had high hopes that we could stop the SPMS progression as well as the Myeloma. It slowed the SPMS progression for a while but now it is progressing at a more rapid pace. Will there be some difference in what they are doing at Tisch? vs what I had done. Did my stem cells not work for some reason? Just trying to understand what might the difference be. Thank you.

It sounds like the procedure you underwent was HSCT, where chemotherapy drugs are used to first wipe out your immune system, and then a stem cell transplant "reboot" your immune system, in theory putting into autoimmunity.

This is very different from what Dr. Sadiq is doing. Dr. Sadiq's stem cells don't really affect the immune system, they are meant instead to repair the damage that the MS disease process does to the central nervous system. Two entirely different approaches. Dr. Sadiq's protocol doesn't really effect the MS disease process, just the damage done by it.

HI man, what do you think about this study: “Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis,” which was published on March, 9 2018 in the Journal of Translational Medicine.Researchers at the Stem Cell Institute in Panama have now completed a one-year Phase 1/2 clinical study (NCT02034188) to test the effectiveness and safety of umbilical cord MSCs for the treatment of MS.

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Regretfully, due to the high volume of e-mail received and the realities of living with progressive MS, I'll no longer be able to respond to all e-mails sent. I do read each note, and will do my best to answer as many messages as I can.

About Me

I'm Marc, a 53-year-old male, living in New York City with my lovely and wonderful wife Karen. Diagnosed with Primary Progressive Multiple Sclerosis in March of 2003, I now require a wheelchair to get around the city. I like to drive the wheelchair at full speed, thus the moniker "Wheelchair Kamikaze". I've managed to rig a camera to my chair, so I'm able to take videos and still photos from the unique vantage point of a wheelchair, which I intend to post here.
Before getting sick, I was the Director of DVD Production for one of the major international music companies. Yes, I was once a member of the Evil Empire...
Prior to my enlistment in the Evil Empire, I worked as a video producer and editor.
I grew up in New York City, and spent the 1980s in Boston (college and postcollege rock 'n roll craziness). During the 1990s, I lived in South Florida, until I woke up one morning and realized I was living in South Florida, came to my senses, and moved back to New York.
I hope you like my blog...